High-harmonic fast-wave power flow along magnetic field lines in the scrape-off layer of NSTX.

A significant fraction of high-harmonic fast-wave (HHFW) power applied to NSTX can be lost to the scrape-off layer (SOL) and deposited in bright and hot spirals on the divertor rather than in the core plasma. We show that the HHFW power flows to these spirals along magnetic field lines passing through the SOL in front of the antenna, implying that the HHFW power couples across the entire width of the SOL rather than mostly at the antenna face. This result will help guide future efforts to understand and minimize these edge losses in order to maximize fast-wave heating and current drive.

Continuous improvement of H-mode discharge performance with progressively increasing lithium coatings in the National Spherical Torus Experiment.

Lithium wall coatings have been shown to reduce recycling, improve energy confinement, and suppress edge localized modes in the National Spherical Torus Experiment. Here, we show that these effects depend continuously on the amount of predischarge lithium evaporation. We observed a nearly monotonic reduction in recycling, decrease in electron transport, and modification of the edge profiles and stability with increasing lithium. These correlations challenge basic expectations, given that even the smallest coatings exceeded that needed for a nominal thickness of the order of the implantation range.

Thermoelectric magnetohydrodynamic stirring of liquid metals.

The direct observation of a thermoelectric magnetohydrodynamic (TEMHD) flow has been achieved and is reported here. The origin of the flow is identified based on a series of qualitative tests and corresponds, quantitatively, with a swirling flow TEMHD model. A theory for determining the dominant driver of a free-surface flow, TEMHD or thermocapillary (TC), is found to be consistent with the experimental results. The use of the analytical form for an open geometry develops a new dimensionless parameter describing the ratio of TEMHD to TC generated flows.

Evidence for extra-renal 1 alpha-hydroxylation of 25-hydroxyvitamin D3 in pregnancy.

The kidneys are thought to be the only organs capable of 1 alpha-hydroxylation of vitamin D and its metabolites. We have examined the in vivo conversion of 3H-(25,26)-25-hydroxyvitamin D3(25OHD3) to 3H-(25,26)-1 alpha,25-dihydroxyvitamin D3 [1 alpha,25(OH)2D3] in vitamin D-deficient, pregnant and nonpregnant rats. As expected, nephrectomy of nonpregnant, vitamin D-deficient rats prevented the conversion of 25OHD3 to 1 alpha,25(OH)2D3. In contrast, nephrectomy of pregnant, vitamin D-deficient rats reduced but did not abolish the formation of 1 alpha,25(OH)2D3 from its precursor. The identity of the radioactive metabolite formed from 3H-25OHD3 which circulated in nephrectomized, pregnant rats was established as 1 alpha,25(OH)2D3 by comigration with synthetic 1 alpha,25(OH)2D3 on high-pressure liquid chromatography. The simultaneous absence of 1 alpha,25(OH)2D3 in the fetal kidneys indicated that the site of 1 alpha-hydroxylation after nephrectomy of the pregnant rat was probably extra-renal in origin. Two sites of 1 alpha-hydroxylation of 25OHD3, one renal and the other extra-renal, either fetoplacental or maternal, may exist in the pregnant, vitamin D-deficient rat.

Vitamin D and pregnancy: the maternal-fetal metabolism of vitamin D.

A model of the maternal-fetal metabolism of vitamin D3 is depicted in Fig. 2. 25-OHD3 of maternal origin is metabolized by the maternal kidneys to the potent metabolite, 1,25-(OH)2D3, which acts on the maternal intestine, kidneys, and skeleton. The maternal kidneys and other organs can produce 24,25-(OH)2D3, although this pathway may be suppressed near the end of gestation. The placenta has selective permeability to the vitamin D3 metabolites, with 25-OHD3 crossing from the mother to the fetus more readily than the dihydroxylated metabolites. The onset of the placental synthesis of 1,25-(OH)2D3 during gestation is unknown. Likewise the regulation of the placental 25-OHD3-1 alpha-hydroxylase is unknown. 1,25-(OH)2D3 of placental origin may enter the maternal or the fetal circulation or act locally on the placenta by inducing the synthesis of proteins involved in the cellular transport of Ca. Perhaps one placenta cell type synthesizes 1,25-(OH)2D3 and another cell type possessing a cytoplasmic receptor for 1,25-(OH)2D3 responds to this metabolite. The function of the 24,25-(OH)2D3 produced by the placenta is unknown. The concentration of free 25-OHD3 and free 1,25-(OH)2D3 in the fetal circulation exceeds the maternal levels due to the differences in the DBP concentrations of the two bloodstreams. The 1,25-(OH)2D3 in the fetal bloodstream may originate from either the placenta or the fetal kidneys. The latter site may not be active in utero due to the hypercalcemia and hyperphosphatemia relative to the maternal levels of these ions. 1,25-(OH)2D3 in the fetal bloodstream acts on those fetal tissues containing cytoplasmic receptors for this metabolite. The intestinal mucosa apparently lacks these receptors until sometime during neonatal life. In contrast, fetal bone cells possess receptors for the 1,25-(OH)2D3. The 24,25-(OH)2D3 in the fetal bloodstream may also be involved in the growth and differentiation of the fetal skeleton. However, the precise role of both metabolites in the fetus remains conjectural.

Integrated plasma facing component calorimetry for measurement of shot integrated deposited energy in the NSTX-U.

The upgrade to the National Spherical Torus eXperiment (NSTX-U) [J. Menard et al., Nucl. Fusion 52, 083015 (2012)] increases the injected neutral beam power up to 12 MW and the plasma current up to Ip = 2 MA for plasma durations up to 5 s. The graphite plasma facing components have been re-designed to handle greater heat and energy fluxes than were seen in NSTX using a castellated design. We present the experimental testing and validation of a castellated graphite target, similar to the prototype tile design, instrumented with thermocouples at various depths in the castellation. During testing, incident heat flux is provided by a programmed electron beam system and surface temperatures are measured via infrared thermography directly viewing the target surface. It was found that the thermocouple response scaled linearly with the measured surface temperature rise regardless of thermocouple depth in the castellation. A sensitivity of 14.3 °C/kJ of deposited energy was found when treating individual castellations as a semi-infinite solid.

Experimental tests of an infrared video bolometer on Alcator C-Mod.

A prototype of an infrared imaging bolometer (IRVB) was successfully tested on the Alcator C-Mod tokamak at the end of its 2016 campaign. The IRVB method interprets the power radiated from the plasma by measuring the temperature rise of a thin, ∼2 µm, Pt absorber that is placed in the torus vacuum and exposed, using a pinhole camera, to the full-spectrum of plasma's photon emission. The IRVB installed on C-Mod viewed the poloidal cross section of the core plasma and observed Ohmic and ion cyclotron range of frequency (ICRF)-heated plasmas. Analysis of total radiated power and on-axis emissivity from IRVB is summarized, and quantitative comparisons made to data from both resistive bolometers and AXUV diodes. IRVB results are clearly within a factor of two, but additional effort is needed for it to be used to fully support power exhaust research. The IRVB is shown to be immune to electromagnetic interference from ICRF which strongly impacts C-Mod's resistive bolometers. Results of the bench-top calibration are summarized, including a novel temperature calibration method useful for IRVBs.

Thyrocalcitonin and the jejunal absorption of calcium, water, and electrolytes in normal subjects.

Jejunal absorption of calcium, water, and electrolytes was measured in 10 normal subjects by the triple-lumen perfusion method. During the control period, water and electrolyte movements were minimal when a bicarbonate-free test solution was infused. By contrast, bicarbonate-containing solutions were readily absorbed in the control period. Intravenous infusion of synthetic salmon calcitonin (SCT) (1 Medical Research Council U/kg wt/h) over 110-120 min resulted in a marked jejunal secretion of water, sodium, potassium, and chloride in 8 of the 10 subjects. This jejunal secretion occurred with both the bicarbonate-free and the bicarbonate-containing test solutions. Calcium absorption was not affected by SCT, and the serum calcium concentration did not fall during SCT infusion. These results suggest that diarrhea in patients with medullary carcinoma of the thyroid may be due to intestinal secretion secondary to high blood concentrations of thyrocalcitonin.

Lymphokine-induced monocytic differentiation as a possible mechanism for hypercalcemia associated with adult T-cell lymphoma.

Patients with adult T-cell lymphoma frequently have hypercalcemia. Bone biopsies from these patients show increased numbers of osteoclasts. We hypothesized that substances produced by the malignant T-cell caused these phenomena by increasing the formation and/or activity of osteoclasts. To test this hypothesis, we cultured U937 cells in conditioned media from a clonal T-cell line derived from a patient with adult T-cell lymphoma and hypercalcemia. This conditioned media produced maturational changes in the U937 cells as evidenced by decreased proliferation, increased adherence, increased expression of complement receptors, and formation of multinucleated giant cells. These changes were synergistically enhanced by the addition of 1 alpha, 25-dihydroxyvitamin D3 which is known to promote monocyte differentiation. We also tested interleukin 2 and gamma- and alpha-interferon to see if they were responsible for the maturational changes. Although some effects were seen, these lymphokines could not account for all the changes induced by the T-cell conditioned media. These findings support the above hypothesis and suggest that other unidentified factors may promote the differentiation of osteoclast precursors and be involved in the pathogenesis of the hypercalcemia.

Design and characterization of a prototype divertor viewing infrared video bolometer for NSTX-U.

The InfraRed Video Bolometer (IRVB) is a powerful tool to measure radiated power in magnetically confined plasmas due to its ability to obtain 2D images of plasma emission using a technique that is compatible with the fusion nuclear environment. A prototype IRVB has been developed and installed on NSTX-U to view the lower divertor. The IRVB is a pinhole camera which images radiation from the plasma onto a 2.5 µm thick, 9 × 7 cm2 Pt foil and monitors the resulting spatio-temporal temperature evolution using an IR camera. The power flux incident on the foil is calculated by solving the 2D+time heat diffusion equation, using the foil's calibrated thermal properties. An optimized, high frame rate IRVB, is quantitatively compared to results from a resistive bolometer on the bench using a modulated 405 nm laser beam with variable power density and square wave modulation from 0.2 Hz to 250 Hz. The design of the NSTX-U system and benchtop characterization are presented where signal-to-noise ratios are assessed using three different IR cameras: FLIR A655sc, FLIR A6751sc, and SBF-161. The sensitivity of the IRVB equipped with the SBF-161 camera is found to be high enough to measure radiation features in the NSTX-U lower divertor as estimated using SOLPS modeling. The optimized IRVB has a frame rate up to 50 Hz, high enough to distinguish radiation during edge-localized-modes (ELMs) from that between ELMs.

Preliminary design of a tangentially viewing imaging bolometer for NSTX-U.

The infrared imaging video bolometer (IRVB) measures plasma radiated power images using a thin metal foil. Two different designs with a tangential view of NSTX-U are made assuming a 640 × 480 (1280 × 1024) pixel, 30 (105) fps, 50 (20) mK, IR camera imaging the 9 cm × 9 cm × 2 µm Pt foil. The foil is divided into 40 × 40 (64 × 64) IRVB channels. This gives a spatial resolution of 3.4 (2.2) cm on the machine mid-plane. The noise equivalent power density of the IRVB is given as 113 (46) µW/cm2 for a time resolution of 33 (20) ms. Synthetic images derived from Scrape Off Layer Plasma Simulation data using the IRVB geometry show peak signal levels ranging from ∼0.8 to ∼80 (∼0.36 to ∼26) mW/cm2.

Calcitriol levels in hypercalcemic patients with adult T-cell lymphoma.

Hypercalcemia is a frequent complication in patients with adult T-cell lymphoma. We measured serum calcitriol (1,25-dihydroxyvitamin D3) levels in five hypercalcemic patients with adult T-cell lymphoma and compared the values with those of five patients with mycosis fungoides, a T-cell neoplasm not associated with hypercalcemia. All five patients with adult T-cell lymphoma had calcitriol levels in or below the normal range. These data show that elevated calcitriol levels are not uniformly elevated in this disorder and may not be the usual cause of hypercalcemia in this subgroup of patients with lymphoma.

Correlation between low levels of estrogen receptors and estrogen responsiveness in two rat osteoblast-like cell lines.

With the knowledge that estrogen replacement therapy can circumvent postmenopausal osteoporosis and with the discovery of estrogen receptors (ER) in cultures of normal osteoblast-like cells, extensive investigations have been directed toward understanding the role of the ER in normal bone homeostasis. ROS 17/2.8 and UMR-106-01, two established osteoblast-like cell lines derived from rat osteosarcomas, have been shown to have estrogen-regulated biologic responses. Only the ROS 17/2.8 cell line has been reported to contain ER. In this study, high-affinity, saturable binding sites characteristic of the ER were detected in UMR-106-01 cells by binding assays with the high-affinity ligand, [125I]17 beta-estradiol. An initial immunoconcentration step before western blot analysis also allowed detection of the full-length ER protein. In addition, northern blot analysis indicated that the entire ER transcript was expressed and that the half-life of the ER message was increased following cycloheximide treatment. Message levels were also regulated by removal of serum and treatment with estradiol. An estrogen-regulated reporter vector, ERET81CAT, was transfected into the UMR-106-01 cells to determine whether the detected level of ER was transcriptionally functional. Using this assay, estrogen responsiveness was evident; however, the response was inconsistent. Multiple factors, such as serum, estradiol, and cell density, influence the ER levels in these cells and probably cause fluctuations in the abundance of receptors available to induce the CAT response. When the cells are responsive, the ICI 164,384 antagonist could block the estrogen-induced activation of CAT.(ABSTRACT TRUNCATED AT 250 WORDS)

Biological activity of 19-nor, 10-keto, 25-hydroxyvitamin D3.

19 nor, 10 keto, 25-hydroxyvitamin D3 (19/10-25OHD3) is a metabolite of 25-OHD3 produced in vitro by various phagocytes including normal human blood monocytes and transformed cell lines, U937 and HL-60. We recently reported that 19/10-25OHD3, induced differentiation of U937 cells. In these studies, 19/10-25OHD3 alone produced no detectable effect on the growth rates, surface adherence, and oxidative metabolism of U937 and HL-60 cells. When combined with lymphocyte-conditioned medium (LCM), 19/10-25OHD3 reduced proliferation, increased surface adherence and stimulated luminol-dependent luminescence (LDL) of the U937 cells. In contrast, the combination of 19/10-25OHD3 and LCM had no effect on the growth of HL-60 cells but did increase the surface adherence and the expression of a complement receptor component. 19/10-25OHD3 competed for tritium-labeled 1,25(OH)2D3 binding to receptors extracted from cultured human skin fibroblasts. This displacement capacity was 600 times weaker than that of unlabeled 1,25(OH)2D3. Incubation of human skin fibroblasts for 24 hr with 19/10-25OHD3 induced 25OHD3-24-hydroxylase activity in the fibroblasts. The inductive potency of 19/10-25OHD3 was 1/50 that of 1,25(OH)2D3. These results demonstrate bioactivity of 19/10-25OHD3 in several systems. At least one of these responses, the induction of 25OHD3-24-hydroxylase, is a receptor-mediated event. Some of the other responses may be independent of the cellular receptor for 1,25(OH)2D3. Interestingly, the potency of 19/10-25OHD3 was highest in the receptor-mediated response (1:50) and lower in the other parameters, ranging from 1:100 to 1:600 compared to 1,25(OH)2D3. This range of bioactivity in phagocytes and fibroblasts is presently explained.

17 Beta-estradiol inhibits the oxidative metabolism of U937 cells indirectly via lymphocytes.

The effect of 17 beta-estradiol (E) on the oxidative metabolism of U937 cells was studied. E had no direct effect on the proliferation, surface adherence, or luminol-enhanced luminescence (LEL) of the U937 cells. Exposure of U937 cells to lymphocyte-conditioned medium (LCM) and 1,25-dihydroxyvitamin D3 allowed a maximal LEL response by cells stimulated with phorbol myristate acetate. In contrast, LCM from lymphocytes exposed to E (LCM-E) did not stimulate LEL to the same extent as did an equal volume of LCM. Increasing the E concentration in the lymphocyte medium was associated with a dose-dependent reduction in the LEL response of the U937 cells. Mixing equal quantities of LCM and LCM-E significantly decreased LEL levels. LEL stimulated by LCM, gamma-interferon, or differentiation-inducing factor was reduced by the presence of LCM-E. The inhibitory action of LCM-E was reversible and metabolite specific. 17 alpha-E produced an effect that was only one tenth the magnitude of the E effect. These findings indicate that E can modulate the differentiation of phagocytes indirectly by altering the synthesis and/or secretion of lymphokines.

1,25-Dihydroxyvitamin D3 enhances phorbol ester-stimulated differentiation and protein kinase C-dependent substrate phosphorylation activity in the U937 human monoblastoid cell.

In the U937 human monoblastoid cell line, 1,25-dihydroxyvitamin D3[1,25(OH)2D3] through a specific interaction with the 1,25(OH)2D3 receptor promotes differentiation toward a more mature phenotype. In addition to this direct effect, 1,25(OH)2D3 also potentiates differentiation in response to lymphokines and (Bu)2cAMP. We examined the effect of 1,25(OH)2D3 on phorbol ester-stimulated differentiation. Either preincubation with or simultaneous exposure to 1,25(OH)2D3 enhanced phorbol ester-stimulated differentiation. Over a 72-h period, the increase in phorbol ester responsiveness was dependent on the duration of 1,25(OH)2D3 exposure. Enhancement of phorbol ester-induced differentiation was observed with 1,25(OH)2D3 concentrations ranging from 0.1-10 nM. The 1,25(OH)2D3 vitamin D metabolite was more potent than the 24,25-dihydroxyvitamin D3 and 25-hydroxyvitamin D3 metabolites in potentiating phorbol ester-induced differentiation. Phorbol esters can exert at least a portion of their effects on cellular function by activating protein kinase C. Thus, one mechanism by which 1,25(OH)2D3 could amplify signal transduction leading to potentiation of phorbol ester-stimulated differentiation would be by enhancing phorbol ester-stimulated phosphorylation. To examine this possibility, we measured protein kinase C-dependent substrate phosphorylation in extracts derived from cells pretreated with 1,25(OH)2D3. In extracts derived from cells treated with 1,25(OH)2D3, the protein kinase C-dependent phosphorylation of endogenous U937 substrates stimulated by calcium, phosphatidyl serine, and diolein was increased compared to that observed in vehicle-treated cells. The conditions required for 1,25(OH)2D3 to increase protein kinase C-dependent phosphorylation of endogenous substrates (concentration, duration of exposure, and metabolite specificity) were similar to those required to enhance phorbol ester-stimulated differentiation. Possibly mediating this enhanced phosphorylation was an increase in protein kinase C activity observed in extracts derived from 1,25(OH)2D3-treated cells.

Estrogens modulate the responsiveness of osteoblast-like cells (ROS 17/2.8) stably transfected with estrogen receptor.

Recent studies have demonstrated the presence of estrogen receptor (ER) in both normal human osteoblast-like and osteoblast-like osteosarcoma cells. The number of ER in cultured osteoblastic cells is very low (200-500 sites/cell). This has complicated characterization of the biological role of estrogens in bone cells. To study the responsiveness of bone cells to estrogens, we established osteoblast-like cell lines expressing higher ER levels. ROS 17/2.8, an osteoblastic cell line, was stably transfected with the cDNA encoding for the mouse ER. After a selection period, positive clones were isolated and evaluated for the presence of ER by both Northern blot analysis and ligand binding assays. Using these techniques, we detected a significant increase in the level of both ER transcript and binding compared to that in wild-type cells. The levels of expressed ER protein were similar to those reported in normal human osteoblast-like cells in primary culture (approximately 2000 sites/cell). To test whether the exogenously inserted ER was responsive, both wild-type and ER stably transfected cells were transiently transfected with a reporter construct containing an estrogen-responsive element linked to a truncated thymidine kinase promoter and a chloramphenicol acetyltransferase (CAT) reporter gene. Exposure of the cells to increased concentrations of estradiol induced a slight increase in CAT activity in wild-type cells (approximately 1.5-fold) at maximal stimulation; however, it provoked a clear concentration-dependent increase in CAT activity in the ER stably transfected cells, with a maximal stimulation of approximately 10-fold. This event was receptor mediated, since ICI 164,384, an ER antagonist, blocked the enhancement of estradiol-induced CAT activity, and it was specific, since other steroid hormones did not stimulate CAT activity. Finally, we evaluated the ability of ER to modulate an endogenous estrogen-responsive gene by measuring the activity of the enzyme alkaline phosphatase. In addition, diethylstilbestrol, a synthetic estrogen agonist, increased the activity of both the CAT reporter gene and the endogenous alkaline phosphatase enzyme. In summary, we have established osteoblast-like cells expressing high levels of an exogenously inserted ER, which has characteristics similar to those of the endogenous ER in terms of its Kd. Finally, the exogenous ER regulates both exogenously inserted construct (VITERECAT) and endogenous properties of the cells (enzymatic activity and proliferation).

Absorption of inorganic phosphate in the human jejunum and its inhibition by salmon calcitonin.

The jejunal absorption of inorganic phosphate (P) was studied under basal conditions and during the intravenous infusion of synthetic salmon calcitonin (SCT) in normal subjects. Net P absorption increased as the intraluminal P concentration was raised. At intraluminal P concentrations equal to or above the plasma P level P absorption manifested first order kinetics. At intraluminal P concentrations below the plasma P level, net P absorption was non-linear presumably due to the movement of P from plasma to the lumen down a chemical gradient. A net secretion of water and electrolytes occurred in six normal subjects given SCT (250 ng/kg/hr) while saline infusion instead of SCT had no effect on jejunal absorption. Along with the secretory effect SCT reduced calcium and P absorption by 58% and 62% respectively, without any significant fall in the serum levels of calcium or P. The jejunal response to SCT was reproduced twice in a hypoparathyroid subject showing that endogenous parathyroid hormone was not involved in this effect. Calcium and P absorption were positively correlated with water movement suggesting that the observed changes in calcium and P absorption are due primarily to SCT-induced secretion of water. It is concluded that SCT induces a net secretion of water and ions while simultaneously reducing calcium and P absorption.

Calcium requirement for the lymphokine and vitamin D mediated differentiation of monoblastic U937 cells.

The monocyte-osteoclast hypothesis states that osteoclasts are derived from the differentiation of monocytes. Recently we reported that the U937 cell line, a monoblastic cell of human origin, differentiated to an osteoclast precursor when cultured in the presence of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) and lymphokines. Using this model of monocytic differentiation we have tested the role of calcium (Ca) in the culture medium by the addition of CaCl2 in the presence or absence of EGTA, a chelating agent, on the growth and differentiation of the U937 cells. Increasing the Ca concentration ([Ca]) to 2.0 mM inhibited the differentiation of resting or 1,25(OH)2D3 exposed cells, but had no effect on the cells exposed to lymphokines or lymphokines and 1,25 (OH)2D3. Reducing the [Ca] to 10(-7) M inhibited differentiation but also reduced cell viability. Addition of CaCl2 to medium containing EGTA to produce [Ca] in the range of 10(-5) M to 10(-3) M restored the cellular growth and viability. Inhibition of differentiation associated with the reduced calcium concentration over the range of 10(-5) M to 10(-3) M was not due to growth inhibition. These findings show the importance of the extracellular [Ca] in an in vitro model of monocytic differentiation induced by vitamin D and lymphokines.

Retinoids induce U937 cells to express macrophage phenotype.

The effects of two retinoids, all-trans-retinoic acid (t-RA) and 13-cis-retinoic acid (c-RA) were studied in a model of osteoclast precursors. The model employs the U937 cell line induced to differentiate when incubated with 1 alpha,25-dihydroxyvitamin D3 and conditioned medium from stimulated human lymphocytes. t-RA and c-RA (10(-8) to 10(-6) M) inhibited cellular growth rates and increased surface adherence. However, t-RA and c-RA both partially blocked the differentiation induced by 1,25(OH)2D3 and lymphokines. Thus, retinoids alone promoted the differentiation of U937 cells but partially blocked the differentiation induced by a vitamin D metabolite and lymphokines. These results suggest that vitamins A and D may exert antagonistic effects on the recruitment of osteoclast precursors.